ABSTRACT

An acute ischemic stroke (AIS) is one of the most prevalent cause of disability in the entire world. Stroke either kills or renders a victim crippled for the rest of his/her life depending on the severity of the brain regional ischemic attack. Stroke is an emergency and requires prompt theranostic management. It has been shown that mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient energy to meet the needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally-inherited mitochondrial disorders. There is growing evidence to suggest that NO deficiency occurs in MELAS which results in impaired blood perfusion that contributes to several complications in this disease. NO is synthesized from arginine by NOS, which catalyzes the conversion of arginine to NO and citrulline. Citrulline can be recycled into arginine, and therefore, both arginine and citrulline support NO synthesis. The use of 15N2-arginine and 13C-, 2H4-citrulline stable isotope infusion allows measuring arginine flux, citrulline flux, citrulline-to-arginine flux (which represents the de novo arginine synthesis rate), and arginine-to-citrulline flux, which represents the NO production rate. El-Hattab and Jahoor (2017) recently highlighted the utility of the stable isotope tracer infusion technique in providing additional evidence for NO deficiency in MELAS, adding more insight into the potential mechanisms of NO deficiency in this syndrome for the assessment of the effects of supplementation with the NO donors, arginine and citrulline, on improving NO production in MELAS.